DESCRIPTION: It has been proposed that mammalian cells respond to amino acid deficiency by upregulating their amino acid carriers. The applicant has previously shown that the expression of the high affinity cationic amino acid transporter (cat-1) was increased in amino acid starved cells and was downregulated in amino acid rich medium. The molecular mechanism appears to be post-transcriptional, involving cat-1 mRNA stabilization. The main objective of the current application is to investigate the molecular mechanism by which the cat-1 transporter is regulated by amino acid availability. The proposal will examine the genetic elements of the cat-1 gene and the cellular proteins that coordinate posttranscriptional control. The central hypothesis is that the 3' intronic sequence of the cat-1 gene has cis RNA elements for posttranscription regulation that occurs through tissue specific alternative splicing. This study is expected to contribute to the field of nutrient regulation of gene expression.